Systems and methods for therapeutic application of energy

ABSTRACT

A system for controlling blood pressure includes a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a first limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the first limb of the subject, and an energy application module carried by the wearable interface and configured to apply energy of two or more types to the first limb of the subject.

INCORPORATION BY REFERENCE TO ANY PRIORITY DOCUMENTS

This application is a continuation of U.S. patent application Ser. No.17/706,528, filed on Mar. 28, 2022, now U.S. Pat. No. 11,590,348, whichis a continuation of U.S. patent application Ser. No. 16/288,605, filedon Feb. 28, 2019, now U.S. Pat. No. 11,357,981, which claims the benefitof priority to U.S. Provisional Application No. 62/637,100, filed onMar. 1, 2018, and U.S. Provisional Application No. 62/674,832, filed onMay 22, 2018, all of which are herein incorporated by reference in theirentirety for all purposes. Priority is claimed pursuant to U.S.C. § 120and 35 U.S.C. § 119.

BACKGROUND OF THE INVENTION

Embodiments of the present invention relate to systems and methods forcontrolling blood pressure in living subjects.

SUMMARY OF THE INVENTION

In a first embodiment of the present disclosure, a system forcontrolling blood pressure includes a wearable interface having aninternal contact surface, the wearable interface configured to at leastpartially encircle a first portion of a first limb of a subject, asensing module carried by the wearable interface and configured todetermine at least a change in blood pressure of the first limb of thesubject, and an energy application module carried by the wearableinterface and configured to apply energy of two or more types to thefirst limb of the subject.

In another embodiment of the present disclosure, a system forcontrolling blood pressure includes a wearable interface having aninternal contact surface, the wearable interface configured to at leastpartially encircle a first portion of a limb of a subject, a sensingmodule carried by the wearable interface and configured to determine atleast a change in blood pressure of the limb of the subject, wherein thesensing module includes at least one sensor for determining a flowcharacteristic, and an energy application module carried by the wearableinterface and configured to apply energy to the limb of the subject.

In yet another embodiment of the present disclosure, a method forcontrolling blood pressure of a subject includes providing a system forcontrolling blood pressure including a wearable interface having aninternal contact surface, the wearable interface configured to at leastpartially encircle a first portion of a first limb of a subject, asensing module carried by the wearable interface and configured todetermine at least a change in blood pressure of the first limb of thesubject, and an energy application module carried by the wearableinterface and configured to apply energy of two or more types to thefirst limb of the subject, placing the system on an arm of a patient,measuring blood pressure with the system, and applying energy with thesystem to a median nerve of the subject.

In still another embodiment of the present disclosure, a method forcontrolling blood pressure of a subject includes providing a system forcontrolling blood pressure including a wearable interface having aninternal contact surface, the wearable interface configured to at leastpartially encircle a first portion of a first limb of a subject, asensing module carried by the wearable interface and configured todetermine at least a change in blood pressure of the first limb of thesubject, and an energy application module carried by the wearableinterface and configured to apply energy of two or more types to thefirst limb of the subject, placing the system on an arm of a patient,measuring blood pressure with the system, and applying energy with thesystem to a radial nerve of the subject.

In yet another embodiment of the present disclosure, a method forcontrolling blood pressure of a subject includes providing a system forcontrolling blood pressure including a wearable interface having aninternal contact surface, the wearable interface configured to at leastpartially encircle a first portion of a first limb of a subject, asensing module carried by the wearable interface and configured todetermine at least a change in blood pressure of the first limb of thesubject, and an energy application module carried by the wearableinterface and configured to apply energy of two or more types to thefirst limb of the subject, placing the system on an arm of a patient,measuring blood pressure with the system, and applying energy with thesystem to a ulnar nerve of the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

FIG. 2 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 in a fastened, unexpanded condition.

FIG. 3 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 in a fastened, partially expanded condition.

FIG. 4 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 in a fastened, substantially expanded condition.

FIG. 5 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 in use on the wrist of a user.

FIG. 6 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 during the measurement of blood pressure.

FIG. 7 is a perspective view of the wearable blood pressure controlsystem of FIG. 1 during activation in response to a detected change inblood pressure.

FIG. 8 is a cross-section of the wearable blood pressure control systemof FIG. 1 in use on the wrist of a user.

FIG. 9 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

FIG. 10 is a plan view of a user interface of the wearable bloodpressure control system of FIG. 9 .

FIG. 11 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

FIG. 12 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

FIG. 13 is a perspective view of the wearable blood pressure controlsystem of FIG. 12 in a decoupled state.

FIG. 14 is a flow chart describing a method for controlling bloodpressure in a subject.

FIG. 15 is a perspective view of a wearable blood pressure controlsystem in use on the wrist of a user, according to an embodiment of thepresent disclosure.

FIG. 16 is an exploded view of the wearable blood pressure controlsystem of FIG. 15 .

FIG. 17 is a further exploded view of the wearable blood pressurecontrol system of FIG. 15 .

FIG. 18 is a bottom view of the wearable blood pressure control systemof FIG. 15 .

FIG. 19 is a perspective cut-away view of a sensing module of thewearable blood pressure control system of FIG. 15 .

FIG. 20A is a first exploded view of a pump and bladder assembly of thewearable blood pressure control system of FIG. 15 .

FIG. 20B is a second exploded view of a pump and bladder assembly of thewearable blood pressure control system of FIG. 15 .

FIG. 21 is a plan view of a user interface of the wearable bloodpressure control system of FIG. 15 .

FIG. 22 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

FIG. 23 is a bottom view of the wearable blood pressure control systemof FIG. 22 .

FIG. 24 is an active element array of the wearable blood pressurecontrol system of FIGS. 22 and 23 , according to an embodiment of thepresent disclosure.

FIG. 25 is a perspective view of the active element array of FIG. 24 inuse on the wrist of a user.

FIG. 26 is an active element array of the wearable blood pressurecontrol system of FIGS. 22 and 23 , according to an embodiment of thepresent disclosure.

FIG. 27 is a perspective view of the active element array of FIG. 26 inuse on the wrist of a user.

FIG. 28 is a cross-sectional view of the wearable blood control systemof FIG. 22 , taken through line 28-28.

FIG. 29 is a perspective view of a wearable blood pressure controlsystem, according to an embodiment of the present disclosure.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

Hypertension (high blood pressure) affects a large section of theworld's population, with estimates of between 16% to 37% of thepopulation affected. Hypertension can be persistent or transient, but ineither case, is a significant factor which commonly increases morbidityand mortality, both on its own and in conjunction with other maladies.Hypertension is thought to be a factor in about 18% of deaths worldwide.Hypertension is of concern in all parts of the world, among mostpopulation subgroups. The lowering of mean blood pressure by a smallamount (e.g., about 5 mm Hg or more), can significantly reduce stroke orother cardiovascular events.

A simple, wearable device that can sense increases in blood pressure,and in response, deliver blood pressure lowering therapy is describedherein, according to several embodiments. FIG. 1 illustrates a wearableblood pressure control system 10 configured for placement on the wristof a patient. The wearable blood pressure control system 10 comprises ahousing 12 and a band 14 coupled to an underside 16 of the housing 12.The wearable blood pressure control system 10 is shown in FIG. 1 in anunfastened condition. The band 14 is secured to the underside 16 of thehousing 12 by epoxy or adhesive 18. In other embodiments, the band 14may be secured by fasteners, sewing, fusing, or may slide through slitsor elongate spaces in the housing 12. The band 14 is configured to wraparound the wrist of a user/patient and secure to itself by use of a hookand loop (Velcro®-type) system 20. The loop surface 20 a on an interiorof a portion of the band 14 secures to the hook surface 20 b on anexterior portion of the band 14. The band may be provided in a number ofdifferent sizes to optimize placement on a particularly-sized patient(e.g., small, medium, large or pediatric, adult). An inflatable cuff 22extends around a circumferential path 24 encircling an interior 26 ofthe band 14. In some embodiments, the band 14 may be configured to beworn like a watch or a bracelet, and may be configured to partially orfully encircle a limb (e.g., arm) at a portion (e.g., wrist). The hookand loop system may be replaced in alternative embodiments by a buttonclosure, a snap closure, an adhesive closure, or a magnetic closure.

FIG. 2 illustrates the wearable blood pressure control system 10 in afastened condition, with the loop surface 20 a secured to the hooksurface 20 b. No arm of a user is shown in FIGS. 2-4 in order to bettershow the activity of the inflatable cuff 22. A sensor 28 is carried onan interior face 30 of the band 14, and is configured to sense one ormore cardiovascular parameter, such as heart rate, heart ratevariability, electrocardiogram (ECG), including any measured arrythmias,or blood pressure. In some embodiments, the sensor 28 may comprise apulse wave sensor. The pulse wave sensor may comprise CMOS(complementary metal-oxide-semiconductor) technology. In someembodiments, the sensor 28 may comprise an ultrasound transducer. Theultrasound transducer may comprise two or more piezoelectric elements.The ultrasound transducer may be configured to be operated as a Dopplertransducer. In alternative embodiments, the sensor 28 may comprise oneor more optical sensor for performing photoplethysmography (PPG). Acontroller 32 within the housing 12 is configured to receive signalsfrom the sensor 28. The controller 32 may comprise a microcontroller.The controller 32 may be coupled to a transceiver 34, configured tocommunicate wirelessly to a cellular phone, smart phone, or otherpersonal communication device, including a chip implanted in a user'sbody, or carried on a portion of the user's body or clothing. The datamonitoring, and data analysis, are thus capable of being performedremotely. The controller 32 can be configured to analyze data from thesensor 28 to determine the presence of conditions including bradycardia,tachycardia, atrial arrythmia such as atrial fibrillation or atrialflutter, or ventricular arrythmia such as ventricular tachycardia. Theidentification of any of these phenomena may be based on real timeanalysis of heart rate, heart rate variability, or ECG amplitude. Thesensor 28 may be capable of sensing more than one cardiovascularparameter. For example, the sensor 28 may be configured to sense bloodpressure and heart rate, or blood pressure and heart rate variability,or may be configured to obtain an electrocardiogram and measure bloodpressure. In some embodiments, the sensor 28 may comprise two or moresensors. In some embodiments, the two or more sensor may comprise afirst sensor for measuring a first cardiovascular parameter, and asecond sensor for measuring a second cardiovascular parameter, differentfrom the first cardiovascular parameter.

Changes in heart rate variability, for example a reduction in heart ratevariability, have been shown to have some predictive capability ofmortality after myocardial infarction. A more continual or evencontinuous measurement of blood pressure using the sensor 28 allows anawareness of how the heart responds to the changing environment duringeach day. Rather than focusing on simple lowering average (e.g., mean)blood pressure values, there may be more protection against heartdisease by achieving hour-to-hour, day-to-day controlled blood pressurevalues over time. These data may be used to help physicians make moreinformed decisions relating to the treatment of hypertension, andoverall treatment of the heart. The wearable blood pressure controlsystem 10 is configured to monitor blood pressure throughout the day atdifferent activities (eating, drinking, dieting, fasting, exercising,sleeping, walking, standing). Data obtained by the sensor 28 may be usedintelligently to apply treatment based on specific or custom patientneeds, and may be guided by saved information related to optimum timesto apply the therapy.

The inflatable cuff 22 may be operated as a sphygmomanometer cuff,configured to determine blood pressure of the user. The transceiver 34may comprise a wifi antenna. An actuator 36, coupled to the controller32 is configured to receive signals from the controller 32 to cause theinflatable cuff 22 to expand. The actuator 36 may comprise a pneumaticpump configured to increase air pressure within the inflatable cuff 22.The inflatable cuff 22 is shown in FIG. 2 in a substantially unexpandedcondition. The inflatable cuff 22 in FIG. 3 is shown in a partiallyexpanded condition. The inflatable cuff 22 in FIG. 4 is shown in asubstantially expanded condition. The inflatable cuff 22 may also beexpanded by the controller 32 via the actuator 36 in order to apply atherapeutic compression on the wrist of the patient. In a firstembodiment, the sensor 28 is configured to sense blood pressure, and theinflatable cuff 22 is configured to apply therapeutic compression. In asecond embodiment, the sensor 28 is configured to sense at least oneparameter related to blood pressure, and the inflatable cuff 22 isconfigured to sense at least one parameter related to blood pressure,and to also apply therapeutic compression. In a third embodiment, theinflatable cuff 22 is configured to sense blood pressure and to applytherapeutic compression, and the sensor 28 is configured to sense one ormore cardiovascular parameter other than blood pressure. In a fourthembodiment, the sensor 28 is configured to sense at least one parameterrelated to blood pressure, the inflatable cuff 22 is configured to senseat least one parameter related to blood pressure, and some other element(not shown) is configured to apply a therapy for reducing bloodpressure.

In FIG. 5 , the wearable blood pressure control system 10 is in use, inplace on the wrist 38 of the arm 40 of a user 42. The band 14 may besecured immediately adjacent the hand 44 of the user 42, or may beattached around the wrist 38 (or other portion of the arm 40) a distanced away from the hand 44, for example 0.5 cm, 1 cm, 2 cm, 5 cm, 10 cm, or15 cm, or any distance between 0 cm and 15 cm.

Turning to FIG. 8 , wearable blood pressure control system 10 is showncoupled to an arm 40 of the user 42. Anatomical elements such as theradius 49, ulna 51, radial artery 45 and ulnar artery 47 are shown inrelation to the band 14 and housing 12. The positioning of the wearableblood pressure control system 10 in relation to the arm 40 in FIG. 8 isone of many possible choices. The wearable blood pressure control system10 may be oriented differently (e.g., circumferentially/rotationallyand/or longitudinally/axially) if a different juxtaposition between thesensor 28 and one or more of the arteries 45, 47 or between theinflatable cuff 22 and one or more of the arteries 45, 47 is desired. Aninterior 53 of the inflatable cuff 22 is inflated by air pressurized bythe actuator 36, which is free to enter into the housing 12 (or exit outof the housing 12) via a vent hole 55. The air is forced by the actuator36 into the inflatable cuff 22 through an access conduit 57 having avalve 59. The valve 59 is configured to maintain air pressure in theinterior 53 of the inflatable cuff 22. The actuator 36 and/or valve 59are also configured to allow air to exit through the valve 59 when it isdesired to lower the air pressure inside the interior 53 of theinflatable cuff 22.

In FIG. 6 , the sensor 28, in use, senses the blood pressure 46 of theuser 42. The blood pressure 46 may be measured continuously or in aseries of samples. The blood pressure 46 may be treated as a systolicpressure over a diastolic pressure, or may be treated as a mean arterialpressure (MAP). The sensor 28 outputs a signal 48 proportional to theblood pressure 46 that is received by the controller 32. In FIG. 7 , thecontroller 32 commands the actuator 36 to expand the inflatable cuff 22.In embodiments wherein the inflatable cuff 22 is configured to be usedas a sphygmomanometer cuff, the controller 32 controls the inflation ofthe inflatable cuff 22 by the actuator 36 so that the interior 53 (FIG.8 ) is pressurized to a starting pressure P s that is above the expectedmaximum systolic arterial pressure. The controller 32 then commands theactuator 36 and/or valve 59 to allow the release of air from theinterior 53 at a particular rate, so that the pressure of the interior53 is reduced over a time period T to a pressure Pf that is belowexpected minimum arterial diastolic pressure. The oscillometric sensing(e.g., by the sensor 28) of the occlusion and subsequent opening up ofone or more arteries can also be used to determine the actual systolicand diastolic pressures, and the pressurization and depressurization ofthe inflatable cuff 22 can be controlled by these data (e.g., via thecontroller 32).

In embodiments wherein the inflatable cuff 22 is configured to be usedas a therapeutic compression element, the controller 32 controls theinflation of the inflatable cuff 22 by the actuator 36 so that theinterior 53 is pressurized to a desired treatment inflation pressure Pt.The therapeutic compression imparted on the arm 40 by the inflatablecuff 22 can be directed to apply stresses to the median nerve 43 (FIG. 8). Stimulation of the median nerve by application of energy, such ascompression, can help lower blood pressure, via a known neural pathway,which may include the central nervous system (CNS). In some cases, thereduction in blood pressure may be achieved via down-regulation ofsympathetic outflow. In some embodiments, the inflatable cuff 22 may beconfigured to be used both as a sphygmomanometer cuff and as atherapeutic compression element.

FIG. 9 illustrates a wearable blood pressure control system 100configured for placement on the wrist of a patient. The wearable bloodpressure control system 100 comprises a housing 102 and a band 104coupled to an underside 105 of the housing 102. The wearable bloodpressure control system 100 is shown in FIG. 9 in a fastened condition,though without the arm 40 visible, in order to better show features ofthe wearable blood pressure control system 100. A loop 106 is secured toa first portion 108 of the band 104 and a series of rubber wedges 110are carried by a second portion 112 of the band 104. To attach thewearable blood pressure control system 100 to the user's wrist 38, theuser 42 (or a person aiding the user 42) slips first end 114 of the band104 through an opening 116 of the loop 106 and, while applying tractionon the first end 114, pulls one or more of the wedges 110 through theopening 116 of the loop 106, until the band 104 is at a comfortabletightness around the user's wrist 38. A flat edge 118 of one of thewedges 110 a, abuts an edge 120 of the loop 106, locking it in place. Toremove the band 104, the band 104 is forced in the opposite direction,temporarily (elastically) deforming the wedges 110 as they are pulledthrough the opening 116 in the loop 106 (or deforming the loop 106)and/or temporarily (elastically) deforming the loop 106. Alternatively,a hook and loop system 20, like that of the wearable blood pressurecontrol system 10 of FIG. 1 may be used. The wearable blood pressurecontrol system 100 also includes a user interface 101 on a visiblesurface 103 of the housing 102.

The wearable blood pressure control system 100 includes a cuff 122extending circumferentially within the band 104 between a second end 124of the band 104 and the first portion 108. The cuff 122 is secured tothe band 104 along a first edge 126 and a second edge 128, each runningcircumferentially around an internal periphery of the band 104. The cuff122 may be secured to the band 104 at the first and second edges 126,128 by adhesive, epoxy, or hotmelt, or may be sewn, stapled, or securedwith other fastening means. The cuff 122, as named, represents an outerlayer, though it is an inner portion of a circle when attached. As shownin FIG. 9 , the cuff 122 is configured to have an interior space 130that is inflatable.

The cuff 122 carries a pair of sensing elements 132, 134 and a pair ofvibration elements 136, 138. The vibration elements 136, 138 maycomprise piezoelectric crystals, and may comprise quartz, artificialquartz, or PZT (lead zirconate titanate) ceramics. The vibrationelements 136, 138 may be configured to vibrate at ultrasound frequenciesof between about 20 kHz and about 1 MHz, or between about 20 kHz andabout 700 kHz, or between about 20 kHz and about 500 kHz, or betweenabout 25 kHz and about 500 kHz, or between about 30 kHz and about 200kHz, or between about 100 kHz and about 300 kHz. Frequencies betweenabout 20 kHz and about 700 kHz can be very effective at stimulatingnerves, such as the median nerve 43 in the arm 40, or the radial nerveor ulnar nerve. Ultrasound can serve to stimulate several physiologicalprocesses that can aid the reduction of blood pressure. Ultrasoundenergy application is capable of dilating blood vessels, such asarteries, and can thus improve blood perfusion. Via sensory feedback,the brain is signaled, in turn, to modify other physiological functions,to further reduce blood pressure. Thus, the vibration elements 136, 138,when constructed of an appropriate material and having an appropriatethickness to vibrate at one or more frequencies in the 20-700 kHz range,may be configured to stimulate the median nerve 43 via vibration. Theapplied vibration to the median nerve 43 will be sensed in the brain ofthe user 42, which lowers blood pressure accordingly as part of aphysiological feedback loop. The brain is thus “tricked” into playing amore involved interventional role. In some embodiments, one vibrationelement 136 may be configured to vibrate within a lower frequency range(e.g., 20 kHz to 100 kHz) while the other vibration element 138 may beconfigured to vibrate at a higher (ultrasound) frequency range (e.g.,100 kHz to 700 kHz), in order to induce multiple types of effect. Inother embodiments two or more vibration elements 136, 138 may beconfigured to vibrate within a lower frequency range while two or moreadditional vibration elements 136, 138 may be configured to vibratewithin a higher frequency range. In some embodiments, one or morevibration elements 136, 138 may be configured to vibrate at multiplefrequencies, for example a fundamental frequency (or first harmonic) anda second harmonic. The first harmonic, for example, in a particularembodiment may be 150 kHz and the second harmonic may be 300 kHz. Inother embodiments, a third harmonic, or even fourth, fifth, or higherharmonics may be used, as described by the harmonic series. Oneparticular treatment protocol may comprise a first period of activationof the vibration elements 136, 138 which is initiated immediately afterthe sensing elements 132, 134 detect a change (e.g., increase) in bloodpressure. This first period of activation may be followed bypressurization of the cuff 122. In relation to the wearable bloodpressure control system 10 of FIGS. 1-8 , a further embodiment may addthe vibration elements 136, 138. A particular treatment protocolassociated with this alternative embodiment may comprise a first periodof activation of the vibration elements 136, 138 which is initiatedimmediately after the sensor 28 detects a change (e.g., increase) inblood pressure. This first period of activation may be followed by anincrease in pressurization of the inflatable cuff 22. Though the mediannerve 43 is often the target, in other cases, the effect may be focused,or shared, on the radial nerve or the ulnar nerve.

Returning to FIG. 9 , in some embodiments, the sensing elements 132, 134and vibration elements 136, 138 may be replaced by multi-purposeelements which are configured to perform both the sensing function ofthe sensing elements 132, 134 and the energy application function of thevibration elements 136, 138.

One or more of the sensing elements 132, 134 or vibration elements 136,138 may be carried on an outer surface 140 of the cuff 122, or may becarried on an inner surface 142 of the cuff 122, or a combinationthereof. The cuff 122 is configured to maintain the sensing elements132, 134 and vibration elements 136, 138 in proximity to the wrist 38 ofthe user 42 (or other portion of any limb upon which the band 104 hasbeen attached). It may be desired to cover the wrist 38 with an acousticcoupling gel, or other acoustic coupling media, for optimal acousticcoupling between skin of the user 42 and the sensing elements 132, 134or vibration elements 136, 138. The sensing elements 132, 134 andvibration elements 136, 138 can be secured to the outer surface 140and/or inner surface 142 of the cuff 122 by an epoxy or adhesive 144that has appropriate transition acoustic impedance properties. Thewearable blood pressure control system 100 also includes a controller151 and a connection port 191, which will be described in greater detailin subsequent embodiments herein.

FIG. 10 illustrates the user interface 101 which includes a power switch109 configured for turning the wearable blood pressure control system100 on or off. The user interface 101 may comprise a touch screen, andmay utilize capacitive or resistive touch sensitivity. Alternatively,mechanical or membrane buttons/switches may be utilized. A first control111 having a first button 113 and a second button 115 is configured formanually adjusting the vibration mode. In other words, the vibrationelements 136, 138 may be manually set (for example, to low (intensity)vibration, medium vibration, or high vibration) using the first and/orsecond buttons 113, 115. One of the buttons 113, 115 may increase theintensity of vibration, while the other button 113, 115 may decrease theintensity of vibration. Alternatively, an application (App) 153 on amobile phone or device 155 may be configured (via software or firmware)to receive one or more signals 157 from the sensing elements 132, 134,and to automatically adjust the vibration mode, either turning it on oroff, or adjusting it between low, medium, and high vibration. Thevibration mode in some embodiments may be automatically adjustable, viaservo control or other methods, such that the vibration elements 136,138 are caused to activate in a manner which is proportional to ormatches in some way the reduction or increase in amplitude, intensityand/or prevalence of blood pressure changes. For example, the vibrationelements 136, 138 may be configured to operate at a derived function ofthe blood pressure increase that is measured or calculated by thesensing elements 132, 134 (or by the cuff 122 if used as asphygmomanometer cuff).

A second control 117 having a first button 119 and a second button 121is configured for manually adjusting the compression mode. The inflationof the interior space 130 of the cuff 122 may be manually set (forexample, to low inflation, medium inflation, or high inflation) usingthe first and/or second buttons 119, 121. One of the buttons 119, 121may increase the pressure or injected volume of inflation, while theother button 119, 121 may decrease the pressure or injected volume ofinflation. Alternatively, the controller 151 within the housing 102and/or the App 153 may be configured (via software or firmware) toreceive one or more signals from the sensing elements 132, 134, and toautomatically adjust the compression mode, either turning it on or off,or adjusting it between low, medium, and high compression.

FIG. 11 illustrates a wearable blood pressure control system 250 that issimilar to the wearable blood pressure control system 100 of FIG. 9 ,but additionally comprises stimulation electrodes 252, 254, 256 carriedon the outer surface 140 of the cuff 122. The user interface 101 and/orApp 153 may be configured to adjust or program a controller 251 suchthat signals received from the one or more signals from the sensingelements 132, 134 cause current to run through wires or traces 258, 260,262 electrically coupled to the electrodes 252, 254, 256, thus applyingone or more potentials (voltages) across two or more of the electrodes.A current may be applied using voltage control. A current may also beapplied using current control. The applied current is capable ofactivating nerves, such as the median nerve 43, for example, to providean additional input to the brain of the patient. The user interface 101(FIG. 10 ) may include a third mode that is an electrical stimulationmode, also capable of being adjusted manually, or with feedback from thesensing elements 132, 134. Any combination of two or three (or more)modes may be possible, or in some embodiments, only a single mode. Theelectrodes 252, 254, 256 may be configured such that the one or moreapplied potentials are directed to the median nerve 43 to therebystimulate it in order to alter or induce the brain's control ormodification of blood pressure. In alternative embodiments, theelectrodes 252, 254, 256 may be configured to sense physiologicalsignals related to changes in blood pressure or other cardiovascularparameters.

The controller 251 may be configured or programmable to be configured,via hardware, firmware, or software, such that any one or more of theinflation of the cuff 122, activation of the electrodes 252, 254, 256,or activation of the vibration elements 136, 138 is applied with aparticular range of set parameters or set parameter ranges, thus servingas a programmable pulse generator. For example, in certain embodiments,the voltage, current, frequency, or pulse width of the activation of theelectrodes 252, 254, 256 may be controlled within the following ranges.Current: 0.1 mA to 200 mA, or 0.1 mA to 50 mA; frequency/rate ofapplication: 0.1 mA to 200 mA, or 1 Hz to 5,000 Hz, or 1 Hz to 1,000 Hz,or 1 Hz to 200 Hz; pulse width: 0.01 microsecond (μs) to 1000microseconds (μs), or 1 microsecond (μs) to 1000 microseconds (μs), or0.01 microsecond (μs) to 5 microseconds (μs). The controller 251 mayfire the electrodes in a continuous mode, or in random mode comprisingone or more bursts. The on-time of the bursts and the off-time of thebursts may each be independently controlled. A particular program oralgorithm may be used to vary the on-times and off-times. In alternativeembodiments, the controller 251 may be configured or programmable to beconfigured, via hardware, firmware, or software, such that any one ormore of the inflation of the cuff 122, activation of the electrodes 252,254, 256, or activation of the vibration elements 136, 138 is applied inan at least partially random or pseudo-random manner. The human body isadaptable, and many physiological systems tend to adjust to therapeutictreatments, sometimes in a manner that, to the body, appears helpful,when in fact it is antagonistic to the purposes or effects of treatment.Nervous systems are able to continually change by processes such assynaptic adaptation. Adding in random changes to the way the therapeuticelements (cuff 122; vibration elements 136, 138; electrodes 252, 254,256) are applied can serve as a way of getting ahead of or “tricking”the body's adaptation schemes that may otherwise actually proveantagonistic to efforts to control blood pressure. Parameters that maybe adjusted, randomly, or non-randomly, by the controller 251 include:time of application of energy (mechanical, electrical, etc.), length ofinterval of time between application of energy, number of repetitions ofapplication of energy, particular operational frequency of a non-staticmode of energy (e.g., applying ultrasound at varying pulse rates),amplitude of the applied energy, timing of particular combinations ofmore than one element of a particular type of energy, or of two or moredifferent types of energy. Any of these parameters can be increased ordecreased. The controller 251 may be configured to allow theuser/patient to control some or all of these parameter adjustments, forexample, via the user interface 101 and/or App 153. In addition, in someembodiments, there may be security levels to control how much the usercan control: a first level for a user and a second level for aprescribing physician. In some embodiments, the existence of controlsavailable to the physician that are not available to the user may assurea certain amount of randomness in the treatment. This may even benecessary in some cases, for example, for particular patients that donot want to be surprised with a compression, electrode firing, orvibration event. The security levels may include encryption and/orpassword control. The “smart” nature of the wearable blood pressurecontrol system 250, or any of the other systems described in theembodiments herein, allows it to be managed by primary care physicians,ad thus, not requiring a specialist. Also, because the device requiresno surgery or invasive procedure, only a single healthcareperson/location need be involved with the patient's care.

FIG. 12 illustrates a wearable blood pressure control system 300 havingmulti-mode energy delivery therapy including both vibration andelectrical stimulation. The wearable blood pressure control system 300is similar to the wearable blood pressure control system 100 of FIG. 9 ,but does not include compression, and does comprise stimulationelectrodes 302, 304, 306 carried on the limb-facing surface 308 of theband 310. The band 310 has a first end 330 and a second end 332 and isremovably attached to a removable/replaceable housing 336. A loop 334 issecured to the band 310, and has an opening width W₁. An insertionsection 340 of the band 310 has a thickness W₂ that is less than openingwidth W₁. The normal wall 338 of the band 310 has a thickness W₃ that isslightly greater than the opening width W₁, thus creating a frictionfit, which renders wedges 110 or hook/loop 20 a/20 b unnecessary. Inuse, a user inserts the insertion section 340 into the loop 334 andpulls the band 310 from the first end 330 until adjusted to anacceptable amount on the limb of the wearer. The friction between thenormal wall 338 and the loop 334 maintains the band 310 secure. The userinterface 312 and/or App 153 may be configured to adjust or program thecontroller 314 such that signals sent by the controller in response toone or more signals from the sensing elements 316, 318 cause current torun through wires or traces 320, 322, 324 electrically coupled to theelectrodes 302, 304, 306, thus applying one or more potentials(voltages) across two or more of the electrodes. A current may beapplied using voltage control. A current may also be applied usingcurrent control. The applied current is capable of activating nerves,such as the median nerve 43, for example, to provide an additional inputto the brain, which can aid the lowering of blood pressure. The userinterface 312 includes a vibration mode 311 and a stimulation mode 313(via electrode(s)), which are each capable of being adjusted manually,or automatically with feedback from the sensing elements 316, 318. Anycombination of the two modes may be possible, such that a mixed signalmay be created. The mixed signal may include a cycle having a firstperiod of only one of vibration or stimulation and a second period ofthe other of vibration or stimulation. The mixed signal may also includeat least one period of simultaneous vibration and stimulation. Theelectrodes 302, 304, 306 may be configured such that the one or moreapplied potentials are directed to the median nerve 43 to therebystimulate it in order to alter or induce the brain's control ormodification of blood pressure (e.g., lowering blood pressure). Inalternative embodiments, the electrodes 302, 304, 306 may be configuredto sense physiological signals related to changes in blood pressure orother cardiovascular parameters. The combination of vibration andelectrical stimulation working in synchrony can delivery a tailored,optimal result, and can be further informed by the measurement ofcardiovascular parameters such as continuous blood pressure, heart rate,heart rate variability, or ECG, including the detection of particularheart arrythmias.

The controller 314 may be configured or programmable to be configured,via hardware, firmware, or software, such that any one or more of theactivation of the electrodes 302, 304, 306 or activation of thevibration elements 326, 328 is applied with a particular range of setparameters or set parameter ranges, thus serving as a programmable pulsegenerator. For example, in certain embodiments, the voltage, current,frequency, or pulse width of the activation of the electrodes 302, 304,306 may be controlled within the following ranges. Current: 0.1 mA to200 mA, or 0.1 mA to 50 mA; frequency/rate of application: 0.01 Hz to 50kHz, or 1 Hz to Hz, or 1 Hz to 1,000 Hz, or 1 Hz to 200 Hz; pulse width:1 microsecond (μs) to 1000 milliseconds (μs), or 1 microsecond (μs) to1000 microseconds (μs), or 0.01 millisecond (ms) to milliseconds (ms).The controller 314 may fire the electrodes in a continuous mode, or inrandom mode comprising one or more bursts. The activation may comprise aparticular initiation time (start time), a particular end time (stoptime), and/or a particular duration. The period of activation of theelectrodes 302, 304, 306 may include one or more of the followingpatterns: a biphasic sine wave, a multiphasic wave, a monophasic sinewave, a biphasic pulsatile sine wave, a biphasic rectangular wave, amonophasic square wave, a monophasic pulsatile rectangular wave, abiphasic spiked wave, a monophasic spiked wave, and a monophasicpulsatile spiked wave. The one-time of the bursts and the off-time ofthe bursts may each be independently controlled. A particular program oralgorithm may be used to vary the on-times and off-times. In alternativeembodiments, the controller 314 may be configured or programmable to beconfigured, via hardware, firmware, or software, such that any one ormore of the activation of the electrodes 302, 304, 306 or activation ofthe vibration elements 326, 328 is applied in an at least partiallyrandom or pseudo-random manner, as described in relation for theembodiment of FIG. 11 . Any one of the electrodes 302, 304, 306 mayserve as a patient return electrode, thus making unnecessary anadditional skin-placed return electrode patch. Thus, the simple couplingof the band 310 on the limb of the wearer/user allows the wearer/user toimmediately begin using the wearable blood pressure control system 300.

Multiple touch points are provided by the electrodes 302, 304, 306 andvibration elements 326, 328, which are located at different clocklocations around the limb-facing surface 308 of the band 310, thusallowing for a high success rate, as an optimal anatomical location foreffective therapy is more likely to be identified and treated. Thecontroller 314 may be configured to allow the user/patient to controlsome or all of these parameter adjustments, for example, via the userinterface 312 and/or App 153. In addition, in some embodiments, theremay be security levels to control how much the user can control: a firstlevel for a user and a second level for a prescribing physician. In someembodiments, the existence of controls available to the physician thatare not available to the user may assure a certain amount of randomnessin the treatment. This may even be necessary in some cases, for example,for particular patients that do not want to be surprised with anelectrode firing, or vibration event. The security levels may includeencryption and/or password control. A connection port 191 may be used totemporarily or permanently attach a USB cable, USB drive, or othercables or drives, for transferring information, charging internalbatteries, or supplying power to any internal components. Many of thecomponents described in the wearable blood pressure control system 300have relatively low power requirements, thus being amenable to achargeable battery system. The connection port 191 may also be used toattached a wireless antenna, if needed, whether or not there is internalwireless capability within the wearable blood pressure control system300. The communication can allow the wearable blood pressure controlsystem 300 to be controlled by an application on a mobile device, suchas a mobile telephone/smartphone. Data monitoring and analysis can alsobe done remotely at one or more sites.

The wearable blood pressure control system 300 may include adaptivecapabilities. For example, the controller 314 may be programmable, orpre-programmed, to provide a particular therapy plan, such as a morningapplication of energy, a mid-day application of energy, and an eveningapplication of energy. However, by analyzing changes in one or morecardiovascular parameters measured by the sensing elements 316, 318, thecontroller 314 may be configured to change the therapy plan to optimizepatient response. For example, the change may include a larger amplitudeand/or longer duration of the application of vibrational energy and asmaller amplitude and/or shorter duration of the application ofelectrical stimulation energy. Or, in other cases, the change mayinclude a larger amplitude and/or longer duration of the application ofelectrical stimulation energy and a smaller amplitude and/or shorterduration of the application of vibrational energy. An energy modulationalgorithm may be applied, to allow the wearable blood pressure controlsystem 300 to learn to better deliver custom neuromodulation managementto each wearer, which may correspond to each patient's blood pressure orother cardiovascular parameter. The wearable blood pressure controlsystem 300 is thus able to learn from the physiology and treatmenteffect of each patient for a personalized and optimized treatment. Eachindividual energy modality (application of electrical stimulation orapplication of vibration) can be optimized, and the combination of morethan one energy modality can also be optimized. Beat-to-beat intervalsused in the calculation of heart rate or heart rate variability may bederived from ECG data or from blood pressure data. In some embodiments,an RR interval (from successive R points in the QRS complex of the ECG)is used. RR Intervals are sometimes called NN intervals when referringto an RR interval in a normal beat of the heart, or more particularly,beats of the heart not including beats not originating in the sinoatrialnode. In some embodiments, time-domain methods may be used forbeat-related calculations. In other embodiments, geometric methods maybe used for beat-related calculations. In other embodiments, frequencydomain methods may be used for beat-related calculations.

In FIG. 13 , the housing 336 has been removed from the band 310. Thehousing 336 is removeable from and reattachable to the band 310 formultiple reasons. The housing 336 may include one or more rechargeablebatteries which can be recharged by attachment of a power cable to theconnection port 191, or to another port, connected to the batteries. Thebatteries may be rechargeable by wired or by wireless methods, includinginductively-coupled charging. A wireless charging unit 345 may also beused to charge the batteries. In alternative embodiments, one or more ofthe batteries may be a primary cell, configured to be used and discarded(or recycled). The housing 336 is secured to the band 310 via twomagnets 346, 348 which are configured to attract magnets 350, 352carried on a surface 344 of the band 310. In the embodiment of FIG. 13 ,magnet 348 has an externally-facing positive pole which is configured tomagnetically engage with magnet 350, which has an externally-facingnegative pole. Magnet 346 has an externally-facing negative pole whichis configured to magnetically engage with magnet 352, which has anexternally-facing positive pole. The magnets may comprise rare earthmagnets, such as neodymium-iron-boron or samarium cobalt. Theneodymium-iron-boron magnets may be chosen from a grade of N30 orhigher, or N33 or higher, or N35 or higher, or N38 or higher, or N40 orhigher, or N42 or higher, or N45 or higher, or N48 or higher, or N50 orhigher. In some embodiments, the neodymium-iron-boron magnets may have agrade between N30 and N52, or between N33 and N50 or between N35 andN48. In some embodiments one of the two magnets in each attractive pairmay be replaced by a magnetic material such as iron, or 400-seriesstainless steel, which can be attracted by a pole of the opposingmagnet.

Electrical connection may be achieved by conductive projections 354carried on the band 310 and which are configured to conductively engagewith conductive depressions 356 carried on the bottom surface 342 of thehousing 336. The conductive depressions 356 are electrically connectedto the various electrical components of the housing 336, which mayinclude the user interface 312, the controller 314, and the connectionport 191. The conductive projections 354 are electrically connected tothe traces 320, 322, 324 and stimulation electrodes 302, 304, 306, thevibration elements 326, 328, and the sensing elements 316, 318 (FIG. 12). Thus, when the housing 336 is attached to the band 310 via theattraction of the magnets 346, 348, 350, 352, the conductive projections354 are electrically coupled to the conductive depressions 356. The userinterface 312, the controller 314, and the connection port 191 arethereby electrically interlinked with the traces 320, 322, 324 andstimulation electrodes 302, 304, 306, the vibration elements 326, 328,and the sensing elements 316, 318. A user may choose to remove thehousing 336 from the band 310 for other reasons than recharging. Forexample, a first housing 336 may be replaced by a second housing 336, ifthe first housing 336 is damaged or ceases to function. The housing 336may be removed to present to a medical facility, which may upload ordownload information or software revisions, or for maintenance orrepair. The conductive projections 354 and the conductive depressions356 are shown in FIG. 13 between the magnets 350, 352 or magnets 346,348, respectively, but in other embodiments, the conductive projections354 and/or the conductive depressions 356 may be located laterally fromthe magnets 350, 352 and/or magnets 346, 348. In some embodiments, theconductive projections 354 and conductive depressions 356 may each bereplaced by a series of conductive terminals that each have bothprojections and depressions, or by a series of terminals that have asubstantially planar array of conductive terminals (neither projectionsnor depressions).

In alternative embodiments, the magnets 346, 348, 350, 352 may besubstituted by other connections, such as snaps, hooks-and-loops(Velcro®), sliding engagements, or adhesive strips.

A method for controlling blood pressure in a subject is described inrelation to FIG. 14 . In a first step 360 a wearable blood pressurecontrol system 10, 100, 250, 300 is provided. In a second step 362, thewearable blood pressure control system 10, 100, 250, 300 is placed on anarm of the subject. The wearable blood pressure control system 10, 100,250, 300 may be placed in proximity to the median nerve 43. In somecases, the wearable blood pressure control system 100, 250, 300 may beplaced on the right arm in proximity to the right median nerve. In somecases, the wearable blood pressure control system 10, 100, 250, 300 maybe placed on the left arm in proximity to the left median nerve. In somecases, a first wearable blood pressure control system 10, 100, 250, 300may be placed on the right arm in proximity to the right median nerveand a second wearable blood pressure control system 10, 100, 250, 300may be placed on the left arm in proximity to the left median nerve.

In a third step 364, the wearable blood pressure control system 10, 100,250, 300 measures blood pressure of the subject. The blood pressure mayin some cases be measured via a sphygmomanometer cuff, and in othercases, the blood pressure may be measured by a blood pressure sensor. Insome cases, a sensor and a sphygmomanometer cuff may work in conjunctionwith each other to measure blood pressure. The blood pressure measuredmay be presented or analyzed as a systolic pressure over a diastolicpressure, or in other cases may be presented or analyzed as a meanarterial pressure (MAP). In a fourth step 366, if the blood pressure isdetermined to be elevated, or high, or hypertensive, or above apredetermined threshold, the wearable blood pressure control system 10,100, 250, 300 applies energy to the median nerve of the arm on which thewearable blood pressure control system 10, 100, 250, 300 is worn. Theenergy applied may comprise compressive stresses (pressure), orelectrical stimulation, or vibratory stimulation, ultrasonicstimulation, or heat application, or heat removal (cooling), or magneticexposure, or electromagnetic exposure, or sonic stimulation, or othermechanical energy application. In some cases, the application of energyto the median nerve may have duration of between about five minutes andabout one hour, or between about ten minutes and about 45 minutes, orbetween about 15 minutes and about 35 minutes, or between about 20minutes and about 30 minutes, between about one minute and ten minutes,or between about five minutes and about ten minutes. The combination ofenergy application modalities (e.g., vibration and electricalstimulation) can be effective in significantly reducing the timerequired to reduce blood pressure in the patient. Once the increaseblood pressure is sensed, a combination of energy application modalitiescan lower the blood pressure in less than about fifteen minutes, or lessthan about ten minutes, which is significantly faster than traditionalsingle energy modalities.

The wearable blood pressure control system 10, 100, 250, 300 may beconfigured or configured to be programmable so that step 364 (and step366 if determined by the system to be appropriate) occur at particularperiods in the day while the subject wears the wearable blood pressurecontrol system 10, 100, 250, 300. For example, the step(s) may beapplied a) when the subject wakes up or gets out of bed, b) at aparticular time in the morning (e.g., after eating), c) at a particulartime in the middle of the day (e.g., immediately before lunch, duringlunch, or immediately after lunch), prior to going to bed or at someother time in the evening. The wearable blood pressure control system10, 100, 250, 300 may be configured or configurable to perform step 364one, two, three, or more times per day. The wearable blood pressurecontrol system 10, 100, 250, 300 may be configured or configurable toperform step 366 one, two, three, or more times per day.

FIG. 15 illustrates a wearable blood pressure control system 400 havingmulti-mode energy delivery therapy including both vibration andelectrical stimulation. The wearable blood pressure control system 400includes features of the wearable blood pressure control system 250 ofFIG. 11 , the wearable blood pressure control system 300 of FIG. 12 ,and the wearable blood pressure control system 100 of FIG. 9 , as wellas having other distinct features. A housing 402 is connected to a firstband 404 by any of the manners described herein. The first band 404,having a first end 401 and a second end 403, includes an adjustableinternal surface 406 which is configured to be inflated to allow thefirst band 404 to fit onto a wide range of limb sizes (e.g., armcircumference, wrist circumference, etc.). The first band 404 may besecured to itself by a hook and loop system or any of the othermodalities described herein in relation to the other embodiments. Asecond band 408 is carried in parallel with the first band 404 and isconfigured to place a sensing module and/or an energy application modulein proximity to the limb. The sensing module can be configured tomeasure one or more cardiovascular parameters, including blood pressure,electrocardiographic data, heart rate or, heart rate variability fromthe limb. The energy application module may be configured to deliverytwo or more types of energy to the limb, such as vibrational energy orelectrical stimulation energy. A user interface 410 having a display 412and controls 414 is carried on top of the housing 402.

The first band 404, shown in detail in FIG. 16 , comprises an inflatablebladder 416 which is sealed within an upper band 418 and a lower band420. The bladder 416 may comprise a relatively high strength, flexiblematerial such as polyurethane or polyethylene terephthalate (PET). Thebladder 416 may comprise an upper sheet 405 and a lower sheet 407,sealed around a perimeter seal 409. The upper band 418 and the lowerband 420 may comprise a fabric, such as woven polyamide (nylon). Theperimeter 422 of the upper band 418 is sealed to the perimeter 424 ofthe lower band 420, such that when an interior cavity 426 of the bladder416 is inflated with air, the lower band 420 is forced away in a radialdirection from the upper band 418, except at circumferential seams 428,430 (FIG. 15 ). Thus, a contact surface 432 of the lower band 420 servesas the adjustable internal surface 406, configured to contact the skinof a limb of a user. The perimeters 422, 424 may be sealed to each otherwith hot melt adhesive, thermal bonding, or epoxies or adhesives. Thebladder 416 includes an inlet port 434 for entry of inflation fluid(e.g., air) and an outlet port 436 for exit of the inflation fluid. Eachof the ports 434, 436 has an external diameter 438, an inner diameter440, and tapered snap wings 442, 444, as shown in FIG. 17 . Returning toFIG. 16 , the ports 434, 436 extend through holes 446, 448 of the upperband 418, respectively, such that they are accessible for attachment toa main housing 450 of the housing 402. The bladder 416 is trapped (e.g.,sandwiched) between the upper band 418 and the lower band 420 withoutbeing bonded at the bonding region 454. Thus, the bladder is not overconstrained in relation to the upper band 418 or the lower band 420, andthe outer surfaces of the bladder 416 are able to slide along the innersurfaces of the upper band 418 and lower band 420 as the bladder 416 isinflated. In an alternative embodiment, the bladder 416 includes anupper face 452 having a bonding region 454, at least around itsperiphery 458 or a portion of its periphery 458, that is bonded to anunderside 456 of the upper band 418. The bonding region 454 may besealed to the underside 456 of the upper band 418 by hot melt adhesive,thermal bonding, or epoxies or adhesives.

An attachment pin 460 has a distal end 462 that is attached into a hole466 in a first end 470 of the second band 408 and an increased diameterproximal end 464 configured for removably snapping into one of a seriesof holes 468 in a second end 472 of the second band 408. The second band408 is secured to the first band 404 along a lateral edge 474, as shownin FIG. 18 , such that when the first band 404 and second band 408 aresecured around a limb, a series of active elements 476 are coupled inproximity to the skin of the limb. The securement of the second band 408to the first band 404 may be by stitching, welding, overmolding, orthermal bonding. Returning to FIG. 16 , the active elements 476 comprisefour ceramic piezoelectric discs 478 (478 a-d) and four electrodes 480(480 a-d). The piezoelectric discs 478 may be fully molded within thesecond band 408. The second band 408 may comprise a material thatacoustically couples to the piezoelectric crystals of the piezoelectricdiscs 478, for example, a silicone elastomer. The electrodes 480 areexposed at a contact surface 482 of the second band 408, as shown inFIG. 18 , such that they may directly contact the skin of the user whenthe second band 408 is secured to the limb of the user. An acousticcoupling gel may be used on the contact surface 482 and on theelectrodes 480, to maximize the coupling to the skin of the subject.Turning to FIG. 19 , the second band 404 is shown transparently, suchthat the active elements 476 are visible in their embedded array. Eachpiezoelectric disc 478 a-d has an electrically conductive layer 484 thatmay be sputtered or applied by other forms of deposition. A firstconductor wire 486 and second conductor wire 488 are soldered to theelectrically conductive layer 484 at first bare ends 490, 492. Theconductor wires 486, 488 may include outer insulative jackets 494, 496along most of their lengths. Second bare ends 498, 499 of the conductorwires 486, 488 are configured for electrically coupling to electroniccomponents within the housing 402. Each electrode 480 a-d is soldered toa bare end 497 of a conductor wire 495 having an insulative jacket 493.A second bare end 491 is configured for electrically coupling toelectronic components within the housing 402. The lateral edge 474 ofthe second band 408 includes a plurality of snaps 489 configured forsnapping and securing the insulative jackets 493, 494, 496 of theconductor wires 495, 486, 488, to hold the conductor wires 495, 486, 488in place in relation to the second band 408 and the first band 404, thusholding them in place and providing strain relief.

Returning to FIG. 16 , the main housing 450 includes a main circuitboard 487 and a liquid crystal display (LCD) 485, covered by a glasscover 483. These components are enclosed within the main housing 450 bya cover 481, which is secured to the main housing by screws 479. Theuser interface 410 is adhered to the cover 481 by a shaped adhesivelayer 477. Actuatable buttons 475, 473, 471 coupled to the main circuitboard 487 are accessible via touch buttons 469, 467, 465 of the userinterface 410, and via cutaways 463, 461 in the cover 481 and theadhesive layer 477, respectively. FIG. 17 shows the tactile switches459, 457, 455 that are actuated by pressing the actuatable buttons 475,473, 471, respectively. In alternative embodiments, the user interfacemay include capacitive touch sensitivity or resistive touch sensitivity.A diaphragm pump 453 is carried on an auxiliary circuit board 451,configured for controlling blood pressure measurements. The pump 453 maycomprise a piezoelectric-actuated micropump. A spacer 449 is configuredto separate the auxiliary circuit board 451 from the main circuit board487 for space or cooling concerns, but the main circuit board 487 iselectrically coupled to the auxiliary circuit board 451. Either of thecircuit boards 451, 487 may be fabricated by printing or other massfabrication techniques. Power is provided to the electronic componentsby a battery 447, also contained within the housing 402. In someembodiments, the battery comprises a rechargeable battery. In someembodiment, the battery comprises a lithium ion 3.7 Volt rechargeablebattery. The main circuit board 487 is configured to transfer powerand/or control to the auxiliary circuit board 451. The auxiliary circuitboard 451 is configured to use some of this power to drive the pump 453.A microcontroller 419 is carried on the main circuit board 487, but mayalternatively be carried on the auxiliary circuit board 451. Themicrocontroller 419 may be programmed or programmable to control theoperations of any of the functions of the wearable blood pressurecontrol system 400. The microcontroller 419 may control parameters suchas start time, stop time, rise time, intensity, or any RAM timingparameters (memory timing parameters), such as column address strobe(CAS) latency, row address to column address delay, row pre-charge time,or row active time.

Additional electrodes 445, 443 are carried within circular depressions437, 435 in sides 441, 439 of the main housing 450, respectively. Andare electrically coupled to one or both of the main circuit board 487 orauxiliary circuit board 451. In some embodiments, one or both of thecircuit boards 487, 451 may be configured to receive input from theelectrodes 480 a-d and one or more of the electrodes 445, 443 in orderto obtain electrocardiographic data (ECG). In use, a subject places thewearable blood pressure control system 400 onto a first limb, forexample, by wrapping the bands 404, 408 around the subject's left wrist,and securing them. The subject then initiates an electrocardiographicmeasurement via the user interface 410, and then touches either one ofthe electrodes 445, 443 of the main housing 450 with a finger of thesubject's right hand. The electrodes 480 a-d, 445 (or electrodes 480a-d, 443, or other combinations) together create multiple ECG vectors toallow for useful cardiovascular data. The incorporation of both the leftwrist and the right hand (via at least one finger), provides thebilateral input important for a reliable and physiologically indicativeelectrocardiogram (ECG). In some embodiments, the touching of the fingerto the electrode 445 or electrode 443 automatically initiates theelectrocardiographic measurement, without requiring the use of the touchbuttons 469, 467, 465 of the user interface 410. In some embodiments,the control circuitry can be configured or programmed such that thetouch of one of the electrodes 445, 443 with a finger initiates andmaintains ECG measurement, and the removal of that finger stops ECGmeasurement.

FIGS. 20A and 20B illustrates the connections between the bladder 416and the pump 453. The pump 453 includes an outlet port 371 that issecured into inner cylindrical cavity 375 in the main housing 450. Ano-ring 369 carried around the outlet port 371 provides a seal betweenthe pump 453 and the main housing 450, as the o-ring 369 seals thecommunication between the outlet port 371 and the cavity 375. An exhaustport 367, having an o-ring 365 therearound seals into an innercylindrical cavity 363 in the main housing 450. Thus, air being emptiedfrom the bladder 416 will exit through the auxiliary circuit 451, andinto the interior of the housing 402. A solenoid 361 (FIG. 17 ) carriedon the auxiliary circuit 451 may be controlled by the microcontroller419 to close or open the solenoid 361, to keep air within the bladder416 or allow air to exit the bladder 416. A snapping bracket 399 issecured to the lower side 397 of the main housing 450 by inserting tabs395, 393 of the snapping bracket 399 in slots 391, 389 of the mainhousing 450, respectively, and then tightening a screw (not shown)through a hole 387 in the snapping bracket 399 and into a threaded hole385 in the lower side 397 of the main housing 450. The ports 434, 436 ofthe bladder 416 are snapped into the holes 383, 381, respectively, ofthe snapping bracket 399. The tapered snap wings 442, 444 allow thelead-in of the ports 434, 436 into the holes 383, 381, and secureattachment with the snapping bracket 399 and the main housing 450 (andthus, the housing 402). In some embodiments, the tapers of the taperedsnap wings 442, 444 is only on the lead-in side (as shown), and so thebladder 416 can be attached to the housing 402, but not detached. Inother embodiment, there may also be tapers on the lower sides of thetapered snap wings 442, 444, and so the bladder 416 can be attached toand detached from the housing 402. The bladder 416 and first band 404can thus be configured to be disposable and replaceable in someembodiments. In these embodiments, the first band 404 and second band408 may be removably connectable to each other, for example with snaps,hooks and loops, rib and groove configurations, or adhesive attachment.When the ports 434, 436 are snapped through the holes 383, 381, taperedhubs 379, 377 having the extension of the inner cavities 375, 373sealingly engage into the inner diameters 440 of the ports 434, 436.This completes the sealing communication between the pump 453 and thebladder 416.

The adjustable internal surface 406 of the first band 404 is configuredto automatically inflate to an appropriate size (e.g., by the bladder416 being inflated by the pump 453 with a particular volume of air) suchthat it applies the appropriate amount of snugness (radially-appliedpressure) to the limb at the site of attachment. The microcontroller 419can be programmed or programmable to initiate a bladder inflation cycleusing feedback from any two of the electrodes 480. The electrodes 480may additionally or alternatively be located on the contact surface 432of the lower band 420, instead of only on the second band 408. Twoelectrodes 480 can be configured to measure an impedance of the limbtissue between them. Thus, as the bladder 416 is inflated, the measuredimpedance makes a sudden change (spike) with the two electrodes 480 eachbecome substantially coupled to the skin. This occurs with the twoelectrodes 480 each have at least a nominal normal force against theskin. This sudden change in the impedance measurement when an impedancethrough the limb tissue is being measured, with air no longer animpedance component, can be used by the microcontroller 419 to signalthe pump 453 to stop injecting air into the bladder 416. The bladder 416is now adjusted for the appropriate or desired “fit” of the first band404. In a band 404 Alternatively, the internal pressure of the bladder416 may be measured with an internal pressure transducer (not shown).The bladder pressure can be monitored, and the microcontroller 419 willsignal pump 453 to stop injecting air into the bladder 416 when a spikein the pressure is detected.

The user interface 410 is shown in more detail in FIG. 21 . The display412 includes a first line 433 configured to display a current orlatest-measured value of systolic blood pressure, for example, systolicarterial blood pressure. The display 412 includes a second line 431 fora current or latest-measured value of diastolic blood pressure, forexample, diastolic arterial blood pressure. Alternatively, in place ofthese two lines of text 433, 431, a graph of blood pressure may bedisplayed, with time in the x-axis and pressure in the y-axis. In otherembodiments, the two lines of text 433, 431 may be replaced by a singleline (or may be augmented by an additional line) showing a current orlatest-measured value for mean pressure, for example mean arterialpressure (MAP). The blood pressure may be displayed, whether a value ora graph, by units of mm Hg, or by other units. The display 412 includesa third line 429 for a current or latest-measured value of pulse orheart rate, e.g., beats per minute. A secondary or alternative displaylocation on the display 412 may indicate heart rate variability.

Controls 414 in FIG. 21 are assigned to: an on/off button 465 by which auser turns the user interface 410 on or off; a start/stop button 467, bywhich a user stops or starts a program of treatment application, with orwithout automatic intermittent blood pressure measurement (depending onprogrammed status); and a blood pressure measurement button 469, bywhich a user initiates a blood pressure measurement cycle.Alternatively, the button 469 can be configured to initiate a pulse(heat rate) measurement cycle. Though not shown, an additional buttonmay be configured to notify emergency medical personnel. Alternatively,the holding down of one of more of the controls 414 may achieve thistask. The wearable blood pressure control system 400 may be configuredto communicate with a mobile phone or other mobile device to make thecall to an emergency system, or to a preprogrammed medical professional.Indicator lights 427, which may comprise LEDs, include: an on/off statusindicator 425; an indicator of active status of applied electricalstimulation 423; an indicator of active status of appliedvibration/ultrasound 421; and an ECG indicator 413, which indicates whenECG is being measured. In other embodiments, the ECG indicator 413 mayalternatively be configured to indicate when electrodes are notsufficiently coupling to skin, or may even indicate when the measuredECG is critical or indicates arrythmias in the subject. Any additionalindicator lights 427 may be added to achieve these or other functions.

FIG. 22 illustrates a wearable blood pressure control system 500 havingmulti-mode energy delivery therapy including both vibration andelectrical stimulation. The wearable blood pressure control system 500is configured to be wrapped around a limb of a subject, as shown inFIGS. 25 and 27 . A band 502 having a first end 504 and a second end 506includes an inner-facing side 510 and an outer-facing side 512. The band502 further includes an elastic clasp 508 having a first hook/loop area514 configured to be secured to a second hook/loop area 516. The elasticclasp 508 comprises an elastic sheet configured to stretchlongitudinally, such that the band 502 will fit on a variety of limbdiameters. When the band 502 is secured to the limb, an additional band518 may be secured around the band 502 for additional securement, but insome embodiments, the band 502 alone is utilized. The additional band518 may be similar to the second band 408 of FIG. 19 , though withoutany of the active components (piezoelectric discs 478, electrodes 480).In some embodiments, the additional band 518 may comprise a band 404having a bladder 416. The wearable blood pressure control system 500includes eight conductive hydrogel electrodes 520 carried on theinner-facing side 510 of the band 502, and eight piezoelectric discs 536(FIG. 28 ) embedded below the electrodes 520. The eight piezoelectricdiscs 536 are each acoustically coupled by the hydrogel such that theyare able to be operable when the electrodes 520 are contacting the skinof the user. An adjustable internal surface 406 such as that of thewearable blood pressure control system 400 of FIG. 15 may alternativelybe incorporated, and the two or more of the electrodes 520 may be usedto measure impedance of the limb tissue, for an automatic inflation ofthe bladder 416, and automatic fitting optimization. A multi-terminalconnector 524 includes magnetic clasps 526, 528 that are configured tomagnetically locate a mating multi-terminal (e.g., multi-pin) connector,which may be attached to a smart watch, health tracker, fitness tracker,or a smart phone, or other mobile control system, such as a systemcarried on one's person or on clothing, or as part of the clothing.Multiple contacts 530 allow for various electrical connections in asmall area. Sixteen contacts are shown, but any number is possible,including two to 32, four to sixteen, or six to twelve, for example. Thepins of a multi-pin terminal may include spring-loaded electricalcontact pins.

A receptable 560 is configured for placement of an electronicidentification device, such as an RFID chip, an EPROM, an EEPROM, or aresistor for a Wheatstone Bridge.

Turning to FIG. 28 , disc-shaped conductive hydrogel electrode 520extends from the inner-facing side 510 of the band 502. The hydrogelelectrode 520 can be flexible and stretchable, but these characteristicsare less needed if the electrodes 520 are small. Thus, the size (e.g.,diameter) of the electrodes 520 can be varied, depending on theparticular geometry of the array. The electrode 520 is coupled to afirst surface 534 of a flexible substrate 531 (e.g., polyimide flexcircuit material) via a conductive paint 532. The conductive paint 532is electrically connected to a trace 552 on the first surface 534 of theflexible substrate 531. In some embodiments, the conductive paint 532comprises a silver-silver chloride (Ag—AgCl). In other embodiments, theconductive paint (ink) may comprise copper or gold, or othersilver-based materials. A first portion 542 of a piezoelectric disc 536is bonded to a first trace 546 on a second surface 538 of the flexiblesubstrate 531 with a conductive epoxy 540. The piezoelectric disc 536may comprise a PZT material (lead zirconate titanate(Pb[Zr(x)Ti(1−x)]O3)), or another appropriate ceramic materialconfigured to vibrate in response to an applied voltage. A secondportion 544 of the piezoelectric disc 536 is electrically coupled to aconductive tab 548 which in turn is electrically coupled to a secondtrace 550 on the second surface 538 of the flexible substrate 531. Thus,the electrode 520 is electrically coupled to a circuit on the firstsurface 534 of the flexible substrate and the piezoelectric disc 536 iselectrically coupled to a circuit on the second surface 538 of theflexible substrate 531. The flexible substrate 531 may comprise one ormore thin strips within the band 502 (for example, between an uppersheet 554 and a lower sheet 556 of the band 502 that are bondedtogether. Each element (electrode or piezoelectric) of each of the eightelectrode 520/piezoelectric disc 536 layered pairs 558 may be operatedindependently, or in some instances, both elements of the layered pair558 may be operated in unison.

The electrodes 520 may be electrically connected and arrayed on the band502 in a variety of combinations in order to achieve a particulareffect. In the wearable blood pressure control system 500′ of FIGS.24-25 , the band 502 includes a first row 562 of four anode electrodes520 a and a second row 564 of four cathode electrodes 520 c. When theband 502 is attached to the wrist 38 of a user 42, as in FIG. 25 , eachanode-cathode pair 566 a-d is substantially aligned along the generallongitudinal axis 568 of the median nerve 43, such that the applicationto the skin 570 of a negative charge from the cathodes 520 c and thepositive charge from the anodes 520 a at substantiallylongitudinally-aligned locations 572, 574 is configured to create aneffect on the conductive properties of the median nerve 43. In somecases, the conduction of the median nerve 43 is increased by theoperation of the anode-cathode pair 566 a-d, and in other cases, theconduction of the median nerve 43 is decreased or disrupted by the bythe operation of the anode-cathode pair 566 a-d. In use, a user mayachieve acceptable results with the orientation of the band 502 as shownin FIG. 25 , with a first lateral edge 576 of the band 502 locatedproximally and a second lateral edge 578 of the band 502 locateddistally. In other cases, the results may not be desirable, and the usermy remove and reattach the band 502 such that the first lateral edge 576of the band 502 is located distally and the second lateral edge 578 ofthe band 502 is located proximally, wherein the results are improved.The traces 552, 546, 550 for each electrode 520 and piezoelectric disc536 of the flexible substrate 531 flex circuit 580 (FIG. 28 ) can befabricated in a variety of patterns to achieve different electricalconnections. The contacts 530 of the multi-terminal connector 524 may beassigned independently to also allow for different electrical connectionconfigurations. Though the median nerve 43 is often the target, in othercases, the effect may be focused, or shared, on the radial nerve or theulnar nerve. The band 502 may alternatively be located in otherpositions (around upper arm, around upper forearm) to get the desiredeffect, or even around a portion of the leg.

In the wearable blood pressure control system 500″ of FIGS. 26-27 , theband 502 includes a first row 582 of four common-grounded electrodes 520m and a second row 584 of four electrodes 520 w, 520 x, 520 y, 520 zthat are configured to be excited independently of each other. When theband 502 is attached to the wrist 38 of a user 42, as in FIG. 27 , thecommon-grounded electrodes 520 m are located proximally and each of theindependent electrodes 520 w-z are located distally. Because they areindependently connected with respect to each other, the independentelectrodes 520 w-z can be operated in a wide range of differentpatterns.

In alternative embodiments, the electrodes 520 and piezoelectric discs536 may each have unequal numbers (e.g., six electrodes 520 and fourpiezoelectric discs 536, etc.) or equal numbers. Some pairs 566 mayexist in some portions of the band 502, while single electrodes 520 orsingle piezoelectric discs 536 may exist in other portions of the band502. Though the bands 502 of the wearable blood pressure control systems500, 500′, 500″ are shown without a bladder 416, in other embodiments,each of the wearable blood pressure control systems 500, 500′, 500″ mayincorporate a bladder 416, either for one-size-fits-all sizing, or forsphygmomanometry, or for therapeutic compression. The arrays ofelectrodes 520 and piezoelectric discs 536 presented herein allow formultiple touch points on the skin or around the limb, which can lead toa faster reduction of blood pressure.

In alternative a wearable blood pressure control system 600 isillustrated in FIG. 29 , and includes a housing 602 (similar to housing402) and a band 604. The band 604 has a bracelet-like structurecomprising five individual flex circuit sections 606 a-e. The flexcircuit sections 606 a-e each have conductive tracings 608 coupled tocomponents (e.g., electrodes, piezoelectric elements—not shown). Thecomponents may in some embodiments be arranged as in the layered pair558 of FIG. 28 . A hinge joint 610 between each adjacent flex circuitsection 606 a-e includes one or more conductor 612 linking them togetherelectrically. The hinge joint 610 may in some embodiments include anelastic matrix, to allow some elastic separation and recoil (stretch)between adjacent flex circuit sections 606 a-e. Though five flex circuitsections 606 a-e are shown in FIG. 29 , any number may be used, forexample, between three and sixteen or between four and ten. Thelow-profile and light weight structure of the flex circuit sections 606a-e, as well as the modular architecture and ease of fabrication,increase affordability and allow for an easy to wear system.

While the foregoing is directed to embodiments of the present invention,other and further embodiments of the invention may be devised withoutdeparting from the basic scope thereof. Though not described in detailabove, the wearable blood pressure control system 400 of FIG. 15 , thewearable blood pressure control system 500 of FIGS. 22-23 , and thewearable blood pressure control system 600 of FIG. 29 may also beutilized according to the method described in relation to FIG. 14 .

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “approximately”,“about”, and “substantially” as used herein include the recited numbers(e.g., about 10%=10%), and also represent an amount close to the statedamount that still performs a desired function or achieves a desiredresult. For example, the terms “approximately”, “about”, and“substantially” may refer to an amount that is within less than 10% of,within less than 5% of, within less than 1% of, within less than 0.1%of, and within less than 0.01% of the stated amount.

What is claimed is:
 1. A system comprising: a wearable interface havingan internal contact surface, the wearable interface configured to atleast partially encircle a first portion of a first limb of a subject;an energy application module carried by the wearable interface andconfigured to apply energy of two or more types to the first limb of thesubject, wherein the energy application module comprises a plurality offlexible electrodes configured to be operated such that the plurality offlexible electrodes apply a focused effect on a nerve of the first limbof the subject, wherein the energy application module further comprisesa plurality of piezoelectrics, and wherein at least one of the pluralityof flexible electrodes and at least one of the plurality ofpiezoelectrics comprise a layered pair.
 2. A system comprising: awearable interface having an internal contact surface, the wearableinterface configured to at least partially encircle a first portion of afirst limb of a subject; an energy application module carried by thewearable interface and configured to apply energy of two or more typesto the first limb of the subject, wherein the energy application modulecomprises a plurality of stretchable electrodes configured to beoperated such that the plurality of stretchable electrodes apply afocused effect on a nerve of the first limb of the subject, wherein theenergy application module further comprises a plurality ofpiezoelectrics, and wherein at least one of the plurality of stretchableelectrodes and at least one of the plurality of piezoelectrics comprisea layered pair.
 3. The system of claim 1, further comprising: a sensorcarried by the wearable interface and configured to be in proximity ofthe first portion of the first limb of the subject and to output asignal for determining at least a change in blood pressure of thesubject at the first limb.
 4. The system of claim 1, wherein theplurality of flexible electrodes and the plurality of piezoelectrics areconfigured to contribute to the focused effect on a nerve selected fromthe list consisting of: a median nerve, a radial nerve, and an ulnarnerve.
 5. The system of claim 1, wherein the wearable interface isconfigured to at least partially encircle a leg of the subject.
 6. Thesystem of claim 1, wherein at least one of the plurality of flexibleelectrodes comprises a hydrogel.
 7. The system of claim 2, furthercomprising: a sensor carried by the wearable interface and configured tobe in proximity of the first portion of the first limb of the subjectand to output a signal for determining at least a change in bloodpressure of the subject at the first limb.
 8. The system of claim 2,wherein the plurality of stretchable electrodes and the plurality ofpiezoelectrics are configured to contribute to the focused effect on anerve selected from the list consisting of: a median nerve, a radialnerve, and an ulnar nerve.
 9. The system of claim 2, wherein thewearable interface is configured to at least partially encircle a leg ofthe subject.
 10. The system of claim 2, wherein at least one of theplurality of stretchable electrodes comprises a hydrogel.